Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Southern blot analysis revealed no difference between the DNA from radiation-induced thymic lymphomas and DNA from normal NFS mice. The probes used in the Southern blot analyses used a murine leukemia virus (MuLV) env DNA probe (pXenv), which specifically hybridizes with xenotropic and recombinant viral env genes, and mouse mammary tumor virus (MMTV) DNA probes (MMTV gag-pol, MMTV env, and MMTV LTR). This suggests that radiation leukemogenesis was not associated with gross alteration of the organization of these retroviral genomes. In DNA from radiation-induced thymic lymphoma, there was no indication of gross rearrangement in the common integration site of MuLV, pim-1, or in the common integration sites of MMTV, int-1 and int-2. Dot blot analysis of RNA from radiation-induced thymic lymphomas and normal thymuses demonstrated that there was no substantial difference between them in the expression of retroviral sequences, pim-1, pvt-1, int-1, or int-2, although transcripts that could be hybridized to the retroviral sequences were slightly elevated in some radiation-induced thymic lymphomas. These results show that radiation leukemogenesis does not appear to involve the activation of endogenous type-C and type-B retroviruses.
 ...
PMID:Lack of evidence for the involvement of type-C and type-B retroviruses in radiation leukemogenesis of NFS mice. 169 Apr 35

Adult C57BL/10 mice (H-2b Fv-1b) inoculated with LP-BM5 murine leukemia virus develop a disease which has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. In the present study, we examined the possibility that this murine AIDS (MAIDS) model would be useful for evaluating antiretrovirus drugs in vivo through the use of a well-defined antiretrovirus drug, the reverse transcriptase (RT) inhibitor (H. Mitsuya, K.J. Weinhold, P.A. Furman, M.H. St. Claire, S. Nusinoff-Lehrman, R.C. Gallo, D. Bolognesi, D.W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) 3'-azido-3'-deoxythymidine (AZT). We evaluated the effect of AZT treatment on de novo virus infection as well as on the induction of immunodeficiency by various parameters, including RT activity in serum, splenomegaly, proliferative responses against alloantigens and mitogens, soluble-antigen-presenting cell activity, and immunoglobulin G levels in serum. Our results demonstrated that AZT treatment of C57BL/10 mice infected with LP-BM5 murine leukemia virus efficiently prevented the induction of immunodeficiency if started at the time of virus inoculation. Starting AZT treatment 1 week later provided only a partial protective effect. Starting AZT treatment 2 weeks later was associated with suppression of RT activity in serum but no prevention of immunosuppression. This MAIDS model may allow rapid and cost-effective screening for antiretrovirus drugs targeted against retroviral functions shared between human AIDS and MAIDS, such as those encoded by gag, pol, or env.
 ...
PMID:3'-Azido-3'-deoxythymidine prevents induction of murine acquired immunodeficiency syndrome in C57BL/10 mice infected with LP-BM5 murine leukemia viruses, a possible animal model for antiretroviral drug screening. 169 56

A fragment of the SIVmac251 pol gene was expressed in Escherichia coli as a trpE fusion protein. Analysis of extracts from bacteria containing this expression plasmid revealed the presence of a reverse transcriptase activity dependent on Mg2+ as divalent cation and active on both poly(rA).oligo(dT) and poly(rC.oligo(dG) templates. In comparative studies, the SIV and HIV-1 reverse transcriptases expressed in bacteria displayed very similar high sensitivities to the chain terminator inhibitors AZTTP and ddTTP. The reverse transcriptase of Moloney murine leukemia virus and the DNA polymerase of E. coli were both more resistant to ddTTP, and the E. coli enzyme was significantly more resistant to AZTTP.
 ...
PMID:Expression of enzymatically active reverse transcriptase of simian immunodeficiency virus in bacteria: sensitivity to nucleotide analogue inhibitors. 170 May 44

Glutamine depletion strongly inhibits the replication of Rauscher murine leukaemia retrovirus (RLV) in vitro. Pseudomonas 7A glutaminase-asparaginase (PGA), capable of depleting glutamine and asparagine for prolonged periods, was used to determine the therapeutic effectiveness of glutamine depletion in mice infected with RLV or Friend virus. During PGA treatment of viraemic animals, serum reverse transcriptase activity fell to control levels and infected animals did not develop splenomegaly. The therapeutic results obtained with PGA compared favourably with those of azidothymidine given intraperitoneally at 30 mg/kg/day. Western blots performed on splenic tissue from control and treated animals indicated that glutamine depletion prevented readthrough of an amber codon at the gag-pol junction, stopping translation of viral mRNA at that point. Treatment of RLV-infected animals with PGA resulted in nearly a 200% increase in mean survival time even when therapy was initiated late in the course of the disease. To our knowledge, this is the first demonstration that a nutrient required for viral replication can be enzymically depleted in vivo to inhibit viral replication.
 ...
PMID:Inhibition of mouse retroviral disease by bioactive glutaminase-asparaginase. 170 10

We have previously shown that strong epitopes recognized by anti-Friend virus (FV) cytotoxic T lymphocytes (CTL) in H-2b mice are encoded in both the env and gag/pol regions of the helper friend leukemia virus genome. Two approaches have been used to identify these epitopes. At the nucleic acid level, we have constructed env genes with either of two in-frame deletions: pKR2, an env gene with a 681-bp deletion in the gp70 region and inserted into the pSV2-gpt-1 expression vector; and pKR1, an env gene with an 81-bp deletion in the p15E region and inserted into pSV2-gpt-1. Cell clones were established by transfecting Fisher rat embryo cells with pDb (the H-2Db restriction element), pNEO (for G418 selection) and either pKR1 or pKR2. Db and env gene expression was monitored by immunoprecipitation with polyclonal antibodies or by detection of viral RNA on Northern blots. Expressor cell clones were tested for susceptibility to lysis by polyclonal anti-FV/Db CTL in 51Cr-release assays. Whereas cells expressing pKR1 were lysed to the same extent as cells expressing the intact env gene, cells expressing pKR2 were resistant to lysis, suggesting that all detectable env epitopes are encoded within the 681-bp deletion. Polypeptides representing the two most likely candidate epitopes encoded in this segment were synthesized and tested for their abilities to sensitize FRE cells expressing Db alone for lysis by the CTL. One 17-mer polypeptide, AGTGDRLLNLVQGAYQA [corrected], functioned as a strong CTL epitope in this assay, but the other 18-mer polypeptide was inactive. Studies of the role of this epitope in the immune response to candidate viral vaccines are in progress.
 ...
PMID:Identification of an epitope encoded in the env gene of Friend murine leukemia virus recognized by anti-Friend virus cytotoxic T lymphocytes. 170 62

Expression of the pol gene of the murine leukemia viruses is subject to translational control at the UAG termination codon of the upstream gene gag. Previous experiments have suggested that: i) Moloney murine leukemia virus infection induces a tRNA(Gln)iii) in an in vitro system using the tobacco mosaic virus as template, this tRNA is able to increase readthrough at the UAG codon [1]. Here we demonstrate that, in vivo, Moloney murine leukemia virus infection does not increase translational readthrough at either the tobacco mosaic virus or the Moloney murine leukemia virus UAG stop codons.
 ...
PMID:UAG readthrough is not increased in vivo by Moloney murine leukemia virus infection. 178 22

A murine cell line, EH, expressing the gag and pol proteins of Moloney murine leukemia virus (Mo-MLV) as well as an Mo-MLV recombinant genome with a selectable marker (histidinol dehydrogenase), was transfected with a plasmid coding for the gene of the human T-cell leukemia virus type I (HTLV-I) envelope precursor (gp62), placed under the control of the human cytomegalovirus immediate early promoter. One clone, T. 14, was recovered, in which gp62 RNA and protein were detected. Supernatant from this clone transferred the HisD gene to a panel of cell lines which express receptors for HTLV-I, but was unable to pass the marker gene to cells which do not express receptors. The colony-forming units were sensitive to HTLV-I receptor interference and to specific neutralization by anti-HTLV-I serum. These data show that hybrid virions were produced in which the envelope proteins of HTLV-I had pseudotyped Mo-MLV capside particles containing a selectable recombinant viral genome.
 ...
PMID:A murine cell line producing HTLV-I pseudotype virions carrying a selectable marker gene. 184 35

We have constructed hybrid retrovirus packaging cell lines that express the gibbon ape leukemia virus env and the Moloney murine leukemia virus gag-pol proteins. These cells were used to produce a retrovirus vector at over 10(6) CFU/ml, with a host range that included rat, hamster, bovine, cat, dog, monkey, and human cells. The gag-pol and env expression plasmids were separately transfected to reduce the potential for helper virus production, which was not observed. The NIH 3T3 mouse cells from which the packaging lines were made are not infectable by gibbon ape leukemia virus; thus, the generation and spread of possible recombinant viruses in the packaging cells is greatly reduced. These simian virus-based packaging cells extend the host range of currently available murine and avian packaging cells and should be useful for efficient gene transfer into higher mammals.
 ...
PMID:Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus. 185 8

Six deletion mutations and an insertion were generated in the env gene of cloned copies of Moloney murine leukemia virus DNA. All seven mutants were replication-defective as tested by transformation of NIH/3T3 cells. The mutant DNAs were introduced into NIH/3T3 cells to generate stable producer lines; all released virion particles into the medium, suggesting that none of the mutations affected overall viral gene expression, gag and pol gene expression, gag and pol gene functions, or virion budding. Several of the mutations reduced the lifetime of the env protein or blocked its export to the cell surface. One mutation altering the membrane-spanning region and the cytoplasmic tail of the TM protein had no effect on export of the protein, proteolytic processing, or incorporation into virion particles, but still blocked the infectivity of the resulting virus. The results suggest that alterations in the transmembrane region can affect early steps of infection, such as the fusion of virion and host membranes. Cells expressing this mutant env protein were fully resistant to superinfection by wild-type virus. Thus, induction of virus resistance, presumably reflecting blocking the virus receptor, can be separated from virus infectivity.
 ...
PMID:Analysis of mutations in the envelope gene of Moloney murine leukemia virus: separation of infectivity from superinfection resistance. 185 60

Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides.
 ...
PMID:Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. 845 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>